The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions.
T cells infiltrating inflammatory sites are usually of the activated/memory type. The precise mechanism for the positioning of these cells within tissues is unclear. Adhesion molecules certainly play a role; however, the intricate control of cell migration appears to be mediated by numerous chemokines and their receptors. Particularly important chemokines for activated/memory T cells are the CXCR3 ligands IP-10 and Mig and the CCR5 ligands RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta. We raised anti-CXCR3 mAbs and were able to detect high levels of CXCR3 expression on activated T cells. Surprisingly, a proportion of circulating blood T cells, B cells, and natural killer cells also expressed CXCR3. CCR5 showed a similar expression pattern as CXCR3, but was expressed on fewer circulating T cells. Blood T cells expressing CXCR3 (and CCR5) were mostly CD45RO+, and generally expressed high levels of beta1 integrins. This phenotype resembled that of T cells infiltrating inflammatory lesions. Immunostaining of T cells in rheumatoid arthritis synovial fluid confirmed that virtually all such T cells expressed CXCR3 and approximately 80% expressed CCR5, representing high enrichment over levels of CXCR3+ and CCR5+ T cells in blood, 35 and 15%, respectively. Analysis by immunohistochemistry of various inflamed tissues gave comparable findings in that virtually all T cells within the lesions expressed CXCR3, particularly in perivascular regions, whereas far fewer T cells within normal lymph nodes expressed CXCR3 or CCR5. These results demonstrate that the chemokine receptor CXCR3 and CCR5 are markers for T cells associated with certain inflammatory reactions, particularly TH-1 type reactions. Moreover, CXCR3 and CCR5 appear to identify subsets of T cells in blood with a predilection for homing to these sites.
Qin
S
S
LeukoSite, Inc., Cambridge, Massachusetts 02142, USA. shixin_qin@leukosite.com
Rottman
J B
JB
Myers
P
P
Kassam
N
N
Weinblatt
M
M
Loetscher
M
M
Koch
A E
AE
Moser
B
B
Mackay
C R
CR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers; D054357:Chemokine CXCL10; D018925:Chemokines / Q000276:immunology; D019743:Chemokines, CXC; D002633:Chemotaxis; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019713:Receptors, CCR5 / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015415:Biomarkers; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine